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J Med Genet 2005;42:479-484 doi:10.1136/jmg.2004.030106
  • Original article

Functional polymorphisms in cell death pathway genes FAS and FASL contribute to risk of lung cancer

  1. X Zhang1,2,
  2. X Miao1,
  3. T Sun1,
  4. W Tan1,
  5. S Qu1,
  6. P Xiong1,3,
  7. Y Zhou1,
  8. D Lin1
  1. 1Department of Etiology and Carcinogenesis, Cancer Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
  2. 2Department of Biological Sciences, North China Coal Medical College, Tangshan, Hebei, China
  3. 3Department of Epidemiology, University of Texas M D Anderson Cancer Center, Houston, TX 77030, USA
  1. Correspondence to:
 Dr D Lin
 Department of Etiology and Carcinogenesis, Cancer Institute, Chinese Academy of Medical Sciences, Beijing 100021, People’s Republic of China; dlinpublic.bta.net.cn
  • Received 16 December 2004
  • Accepted 26 January 2005
  • Revised 24 January 2005

Abstract

Background: The FAS and FASL system plays a key role in regulating apoptotic cell death and corruption of this signalling pathway has been shown to participate in immune escape and tumorigenesis. There is reduced expression of FAS but elevated expression of FASL in many types of human cancers including lung cancer. We recently reported an association between functional polymorphisms in FAS (−1377G→A) and FASL (−844T→C) and risk of oesophageal cancer.

Objective: To examine the contribution of these polymorphisms to risk of developing lung cancer.

Methods: Genotypes of 1000 lung cancer patients and 1270 controls were analysed by PCR based restriction fragment length polymorphism. Associations with risk of lung cancer were estimated by logistic regression.

Results: Compared with non-carriers, there was a 1.6 fold excess risk of developing lung cancer for carriers of the FAS −1377AA genotype (odds ratio (OR) 1.59, 95% confidence interval (CI) 1.21 to 2.10; p = 0.001), and 1.8 fold excess risk (OR 1.79, 95% CI 1.26 to 2.52; p = 0.001) for carriers of FASL −844CC. Gene–gene interaction of FAS and FASL polymorphisms increased risk of lung cancer in a multiplicative manner (OR for the carriers of both FAS −1377AA and FASL −844CC genotypes 4.18, 95% CI 2.83 to 6.18). Gene–environment interaction of FAS or FASL polymorphism and smoking associated with increased risk of lung cancer was also found.

Conclusion: These results are consistent with our initial findings in oesophageal cancer and further support the hypothesis that the FAS and FASL triggered apoptosis pathway plays an important role in human carcinogenesis.

Footnotes

  • The first two authors contributed equally to this work.

  • Competing interests: none declared

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